Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic study

Objective: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis. Method: In a naturalistic, ‘single-blind’ design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly. Results: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged. Conclusions: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms.     

The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy

INTRODUCTION: Atypical antipsychotics form a new class of treatment for psychotic disorders that offers advantages over conventional antipsychotics, such as haloperidol. Among these advantages is a lower risk of side effects-in particular movement disorders. The atypical antipsychotics that are currently commercially available are clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. The focus of this report is on the efficacy of quetiapine. DATA SOURCES/STUDY SELECTION: A meta-analysis was performed on three placebo- and five haloperidol-controlled clinical trials of quetiapine. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Scale for the Assessment of Negative Symptoms (SANS). In addition, a responder analysis was performed assessing patients who demonstrated a 40% improvement on the BPRS total score. RESULTS: The results showed that quetiapine was significantly (p<0.05) superior to placebo in improving psychotic symptoms. In addition, quetiapine was not significantly different from haloperidol on measures of efficacy measured by BPRS change score, but was superior to haloperidol in terms of response rate using observed case analysis (but not using last observation carried forward analysis). CONCLUSION: This meta-analysis supports the use of quetiapine as a front-line treatment for schizophrenia.     

An efficacy analysis of olanzapine treatment data in schizophrenia patients with catatonic signs and symptoms

Thirty-five patients suffering from schizophrenia, as diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were preselected from 7 clinical trials according to a priori criteria of catatonic signs and symptoms based on 3 Positive and Negative Syndrome Scale (PANSS) items: scores for PANSS item 19 (mannerism and posturing) and either item 4 (excitement) or item 21 (motor retardation) had to exceed or equal 4 at baseline. This particular patient population represents a severely psychotic sample: mean +/- SD PANSS total scores at baseline were 129.26 +/- 19.76. After I week of olanzapine treatment, mean PANSS total score was decreased significantly (-13.14; p < .001), as was mean PANSS total score after 6 weeks of olanzapine treatment (-45.16; p < .001); additionally, the positive subscale, negative subscale, and mood scores improved significantly. A significant improvement in the catatonic signs and symptoms composite score was also observed at week 6 (-4.96; p < .001). The mean +/- SD daily dose of olanzapine was 18.00 +/- 2.89 mg after 6 weeks of treatment. The present data analysis suggests the efficacy of olanzapine in the treatment of severely ill schizophrenic patients with nonspecified catatonic signs and symptoms.     

Lower levels of whole blood serotonin in obsessive-compulsive disorder and in schizophrenia with obsessive-compulsive symptoms

It has been reported that some schizophrenic patients suffer from obsessive-compulsive symptoms (OCS), and clozapine treatment is quite often associated with an occurrence/increase of OCS in schizophrenic patients. The aim of the study was to explore whether differences would exist in the clinical symptomatology and the whole blood serotonin (5-HT) concentrations in patients with obsessive-compulsive disorder (OCD), schizophrenic patients with and without OCS (S+OCS, S-OCS), and clozapine-treated schizophrenic patients with and without clozapine-induced OCS (CLZ+OCS, CLZ-OCS). We found that S+OCS patients (n=15) showed significantly lower scores on the Hamilton Anxiety Scale (HAMA), but similar levels of compulsions and obsessions using Yale-Brown Obsessive-Compulsive Scale (YBOCS) as compared to the patients (n=35) with OCD. S+OCS patients scored significantly lower on the Positive and Negative Syndrome Scale (PANSS) but higher on the Hamilton Depression Scale (HAMD) compared with S-OCS patients (n=19). However, CLZ+OCS patients (n=15) suffered from dominant compulsions but fewer obsessions compared with the OCD and S+OCS patients. OCD, S+OCS and CLZ+OCS groups had significantly lower levels of whole blood 5-HT than did the healthy volunteers (n=15), S-OCS and CLZ-OCS groups. It suggests that alterations in serotonin metabolism may be a common biological characteristic of OCS in OCD as well as in schizophrenia.     

Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia

OBJECTIVE: The efficacy and safety of olanzapine were compared with those of ziprasidone. METHOD: This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight. RESULTS: The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level. CONCLUSIONS: Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.     

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

OBJECTIVE: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. CONCLUSIONS: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.     

Heart rate dynamics and their relationship to psychotic symptom severity in clozapine-treated schizophrenic subjects

The analysis of heart rate variability (HRV) has proven to be useful in evaluating the neuroautonomic dysfunctions associated with various clinical conditions. The purpose of this study was to investigate the linear and non-linear dynamic measures of HRV, and to evaluate their relationship with the psychotic symptom severity, in clozapine-treated schizophrenic subjects. Fifty schizophrenic patients treated with clozapine as monotherapy and 50 normal control subjects were evaluated for HRV analysis. The HRV measurements were obtained from a 30-min resting electrocardiogram (ECG). The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). In the patient group, the complexity and symbolic dynamics measures as well as the time and frequency domain measures of HRV were significantly lower than in the control group (P<0.01). The intermediate-term fractal scaling component value was significantly higher in the patient group (P<0.01). The PANSS total score and the positive symptom subscale score had significant negative correlations with the sample entropy (SampEn) value (P<0.01). In conclusion, schizophrenic patients treated with clozapine had markedly different heart rate dynamics compared to normal control subjects. The severity of psychotic symptoms was associated with the SampEn value, suggesting that the non-linear complexity measure might be useful in assessing the neuroautonomic dysfunction in schizophrenia.     

Perazine and carbamazepine in comparison to olanzapine in schizophrenia

Atypical antipsychotics like olanzapine are more efficacious in treating negative symptoms and have less side effects. Nevertheless, important adverse effects of olanzapine are, for example, weight gain and hyperglycemia. Perazine in combination with carbamazepine has shown satisfying results in several single-schizophrenia patients, leading to the hypothesis of being equal or even superior to atypical antipsychotic monotherapy. The aim of the present study was to survey the hypothesis that perazine in combination with carbamazepine have an outcome and risk of side effects comparable to olanzapine. Eleven patients with DSM-IV schizophrenia received 14.0 +/- 5.0 mg/day olanzapine and 12 patients received 360.0 +/- 196.0 mg/day perazine in combination with 404.0 +/- 229.0 mg/day carbamazepine. Symptoms and neuropsychological state were assessed 3 times (days 0, 7, 21) using the Positive and Negative Syndrome Scale and the Brief Psychiatric Rating Scale. The neuropsychological state was assessed by the following neuropsychological tests: Benton, d2, ZVT, VLMT and MWT-B. Data were analyzed of variance for multiple dependent variables and repeated-measures multivariate analysis of variance. Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores showed superior improvement in the group receiving olanzapine. Olanzapine offers a more favorable response in positive symptoms than does perazine in combination with carbamazepine. The effect on negative symptoms is favorable in both forms of therapy and no significant differences between the groups could be determined. In both groups, treatment was associated with improved performance in cognitive tests; however, no differences were determined in the effects of the drugs. Results suggest that olanzapine offers a better response in positive symptoms than perazine in combination with carbamazepine.     

Relationship between premorbid functioning and symptom severity as assessed at first episode of psychosis

OBJECTIVE: Investigating the relationship between premorbid and prodromal status and the clinical manifestations of the first psychotic episode is relevant for understanding the pathophysiology of psychosis and for improving management of the disease. This study examined patterns of premorbid functioning of persons interviewed during their first episode of psychotic illness and examined the relationship of premorbid characteristics with symptom severity and cognitive functioning during the first illness episode. METHOD: The data were derived from the baseline assessments of a multicenter international drug trial that enrolled 535 patients in their first episode of psychosis. Subjects' scores on the Premorbid Adjustment Scale were used to assign them to groups according to whether their premorbid functioning was stable-good, stable-poor, or deteriorating. The three groups' scores on the Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, and a cognitive battery were compared. RESULTS: Almost half of the patients (47.5%) had stable-good premorbid functioning, 37.3% had stable-poor premorbid functioning, and 15.1% had initially good, but later deteriorating, premorbid functioning. Compared to the stable-poor and deteriorating groups, the stable-good group had lower (better) negative syndrome and general psychopathology scores on the Positive and Negative Syndrome Scale and a lower CGI severity scale score. Differences between the stable-poor and stable-good groups were also found on some cognitive measures and on the positive syndrome subscale of the Positive and Negative Syndrome Scale. CONCLUSIONS: More than half of the subjects, who were interviewed during their first episode of psychotic disorder, had evident premorbid behavioral disturbances. Poor premorbid functioning before onset of psychosis was associated with more severe symptoms and more severe cognitive manifestations of illness during the first illness episode.     

Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder

CONTEXT: Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance. OBJECTIVE: To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder. DESIGN AND SETTING: Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36). MAIN OUTCOME MEASURES: Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). RESULTS: Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales. CONCLUSIONS: Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.     

奥氮平与氯氮平治疗难治性精神分裂症对照研究

目的评价奥氮平治疗难治性精神分裂症的疗效及安全性。方法将64例难治性精神分裂症患者随机分为研究组和对照组,分别予以奥氮平和氯氮平治疗8周,采用PANSS量表和TESS量表评定疗效和不良反应。结果奥氮平组治疗前后PANSS减分率为39.3%,有效率为72.8%;氯氮平组治疗前后PANSS减分率为36.6%,有效率为59.4%。奥氮平组未见严重的不良反应。结论奥氮平与氯氮平治疗难治性精神分裂症均有良好疗效,奥氮平的副作用小,病人依从性好。     

Neurological soft signs and positive treatment response to olanzapine in chronic schizophrenia

The goal of this study is to examine if Neurological Soft Signs (NSS) scores may improve on an 8-week olanzapine treatment in 10 patients with chronic schizophrenia. The patients were rated every 2 weeks on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale (CGI). Baseline and endpoint NSS scores were evaluated by the Neurological Evaluation Scale (NES). The results demonstrated that baseline total PANSS and subscale scores of positive and general symptomatology, and baseline CGI scores were significantly reduced at the end of olanzapine treatment. There were no significant differences between baseline and endpoint subscale scores of negative symptomatology. We have also found no significant differences between baseline and endpoint total and subscale scores of NES. Baseline total scores of NES were significantly correlated only with negative schizophrenic symptoms at baseline. Our findings indicate that NSS may not improve in schizophrenic patients with olanzapine treatment.     

A randomized, flexible-dose, quasi-naturalistic comparison of quetiapine, risperidone, and olanzapine in the short-term treatment of schizophrenia: the QUERISOLA trial

This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.     

Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial.

BACKGROUND: Selective localization of dopamine D(4) receptors in the prefrontal cortex and preferential affinity of clozapine for the dopamine D(4) receptor over the D(2) receptor led to the hypothesis that the superior efficacy of clozapine may be mediated via blockade of the D(4) receptor. This hypothesis was tested by evaluating sonepiprazole, a selective D(4) dopamine antagonist, in schizophrenia patients. METHODS: We treated 467 hospitalized schizophrenia patients with scores of > or = 60 on the Positive and Negative Syndrome Scale (PANSS) with sonepiprazole, olanzapine, or placebo once daily for 6 weeks. The primary efficacy end point was the mean change from baseline in the PANSS total score at 6 weeks. Secondary efficacy end points were the mean change from baseline in the PANSS factor scores, the Brief Psychiatric Rating Scale score, the Clinical Global Impressions Severity of Illness score, and the Calgary Depression Scale score. RESULTS: No statistically significant differences were observed between placebo and any sonepiprazole dose on the primary or any secondary end point after 6 weeks of treatment. Statistically significant differences, favoring olanzapine over placebo, were observed on all efficacy end points but the Calgary Depression Scale. CONCLUSIONS: Sonepiprazole was ineffective for the treatment of patients with schizophrenia.     

Association of risperidone treatment response with a polymorphism in the 5-HT(2A) receptor gene

OBJECTIVE: This study investigated the effect of the 102-T/C polymorphism in the 5-HT(2A) receptor gene on risperidone efficacy. METHOD: One hundred Han Chinese patients with acutely exacerbated schizophrenia were given risperidone for up to 42 days. The patients were genotyped for 5-HT(2A) polymorphisms. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale while the patients were taking risperidone. Generalized estimating equation methods were used to analyze the effects of treatment duration, T/C genotypes, and other prognostic factors on Positive and Negative Syndrome Scale performance. RESULTS: Patients with the C/C genotype had lower total scores, negative subscale scores, and general psychopathology scores but not positive subscale scores on the Positive and Negative Syndrome Scale than patients with the 102-T/C genotype. Patients with the T/C and T/T genotypes had comparable total and subscale scores. The number of previous hospitalizations and the dose of risperidone also affected Positive and Negative Syndrome Scale total scores. CONCLUSIONS: These results suggest that variations in the 5-HT(2A) receptor gene may influence individual responses to risperidone.     

奥氮平合并氯氮平对男性难治性精神分裂症阴性症状的疗效及安全性的研究

目的观察奥氮平合并氯氮平治疗男性以阴性症状为主的难治性精神分裂症的疗效以及安全性。方法对43例男性原服用氯氮平且以阴性症状为主的难治性精神分裂症患者合并奥氮平5～20mg／d治疗8周,同时于2周内将氯氮平减量且氯氮平剂量2周后不再变化,并于合并治疗前及后2周、4周、8周评定阳性症状与阴性症状量表（PANSS）、副反应量表（TESS）。结果合并奥氮平治疗后2周、4周、8周末PANSS总分和TESS评分较合并前有明显差异。结论奥氮平合并氯氮平对于男性难治性精神分裂症患者的阴性症状有明显的改善,副反应也有减少。     

Combined clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia: clinical and cognitive outcomes

For treatment-refractory schizophrenia, electroconvulsive therapy (ECT) remains controversial because of its cognitive adverse effects. We report here on clinical and cognitive outcomes of a treatment-resistant schizophrenia patient treated with clozapine and right unilateral ECT.The patient was administered 300 mg of clozapine and 12 right unilateral ECT sessions. Psychopathology was rated by means of the Positive and Negative Syndrome Scale. The neurocognitive test battery included the Wisconsin Card Sorting Test, the Münchner Ged?chtnis Test, an attentional performance test, the Trail Making Test, and the Hamburger-Wechsler Intelligence Test.The Positive and Negative Syndrome Scale total score decreased, and all cognitive measures improved.Electroconvulsive therapy would seem to be a safe treatment option for treatment-refractory schizophrenia patients.     

A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia

This double-blind, multicenter study aimed to investigate the efficacy and safety of aripiprazole 10, 15 or 20 mg/day versus placebo. Patients requiring inpatient hospitalization for acute exacerbation of schizophrenia were randomized to once-daily aripiprazole 10, 15 or 20 mg/day or placebo for 6 weeks. The primary efficacy outcome was the mean change from baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total score (last observation carried forward). Patients with no improvement by Week 3 (Clinical Global Impression-Global Improvement score > or =4) could transfer to open-label aripiprazole 20mg/day. In total, 420 patients were randomized to placebo (n = 108); aripiprazole 10 mg/day (n = 106); 15 mg/day (n = 106); or 20 mg/day (n = 100). Of these, 142 patients (34%) completed 6 weeks of treatment, 131 (31%) discontinued to receive open-label aripiprazole, and 147 (35%) for other reasons. Aripiprazole 10, 15 and 20 mg/day each showed significantly greater improvements from baseline than placebo for all efficacy measures, including PANSS Total, Positive and Negative scores, and the CGI-Severity of Illness score. Significantly greater improvements in PANSS Total score versus placebo were achieved by Week 1 with 10 or 20 mg/day and Week 3 with 15 mg/day. All three doses were well tolerated. Overall, aripiprazole was not associated with clinically meaningful differences in extrapyramidal symptoms, prolactin or weight changes versus placebo. Aripiprazole 10 mg/day is effective and well tolerated for patients experiencing an acute exacerbation of schizophrenia.     

Olanzapine in refractory schizophrenia after failure of typical or atypical antipsychotic treatment: an open-label switch study

BACKGROUND: When patients with schizophrenia fail to respond to an atypical antipsychotic, they are sometimes switched to another atypical compound. However, the benefits of such a switch have not been adequately studied. We present an open-label prospective 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder whose treatment resistance to clozapine, olanzapine, risperidone, and haloperidol had been determined prospectively. METHOD: The subjects were 45 inpatients with DSM-IV schizophrenia or schizoaffective disorder who failed to respond to treatment during a 14-week double-blind trial comparing clozapine, olanzapine, risperidone, and haloperidol. The patients had been selected for participation in the double-blind trial on the basis of a history of suboptimal response to previous treatment. Inclusion criteria for the present study were (1) completion of at least 8 weeks of the 14-week double-blind trial, (2) treatment resistance to 1 of the 4 compounds tested as evidenced by a decrease in total PANSS score of less than 20%, and (3) total PANSS score > or = 60. Subjects were cross-titrated from the previous double-blind treatment to open-label olanzapine, 10 to 40 mg/day, and were treated for 14 weeks without concomitant psychotropic medication. Patients were evaluated weekly with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions scale, and Extrapyramidal Symptom Rating Scale. RESULTS: Open-label olanzapine treatment yielded no significant change in PANSS total, positive subscale, or negative subscale scores. There was a significant improvement for the PANSS cognitive factor (mean +/- SD change = 0.92 +/- 2.27; F = 7.5, df = 1,44; p <.009) and a marginally significant worsening for the excitement factor (mean change = -1.36 +/- 4.64; F = 4.0, df = 1,44; p < .053). Nine percent of patients (N = 4) were classified as responders using the Kane et al. criteria. The worsening in the PANSS excitement factor was significantly associated with the length of illness (t = -2.10, df = 44, p < .04). There was a nonsignificant decrease in extrapyramidal side effects and a significant increase in weight (mean increase = 3.5 +/- 6.2 kg [7.8 +/- 13.8 lb]; F = 5.29, df = 1,42; p <.0005). CONCLUSION: Our results indicate that in patients with treatment-resistant schizophrenia, a switch to olanzapine after treatment failure with an atypical agent or haloperidol may not reduce psychopathology in general, but may improve symptoms related to cognitive function.     

Randomized double blind comparison of olanzapine vs. clozapine on subjective well-being and clinical outcome in patients with schizophrenia

OBJECTIVE: This randomized double-blind multicenter trial evaluated the effects of olanzapine vs. clozapine on subjective well-being, quality of life (QOL) and clinical outcome. METHOD: The primary objective was to demonstrate non-inferiority of olanzapine, mean dosage 16.2 +/- 4.8 (5-25 mg/day) vs. clozapine, mean dosage 209 +/- 91 (100-400 mg/day) regarding improvement on the 'Subjective Well-Being under Neuroleptic Treatment' (SWN) Scale after 26 treatment weeks in 114 patients with schizophrenia. Secondary outcome parameters included: Munich QOL Dimension List (MLDL), Positive and Negative Symptom Scale (PANSS), Clinical Global Impression (CGI). RESULTS: SWN scores improved significantly in both groups, olanzapine was non-inferior to clozapine (group difference 3.2 points in favor of olanzapine; 95% CI: 4.2;10.5). MLDL-satisfaction, PANSS and CGI-S improved similarly, olanzapine yielded a higher CGI Therapeutic Index. Individual SWN and PANSS changes correlated only moderately (r = -0.45). CONCLUSION: Olanzapine was non-inferior to clozapine. The lack of a marked correlation between PANSS and SWN improvements indicates that patients and psychiatrists perceive treatment differently.